PHILADELPHIA, July 3, 2007 ? Researchers in Slovakia have
been able to derive mesenchymal stem cells from human adipose, or
fat, tissue and engineer them into “suicide genes” that
seek out and destroy tumors like tiny homing missiles.
This gene therapy approach is a novel way to attack small
tumor metastases that evade current detection techniques and
treatments, the researchers conclude in the July 1 issue of Cancer
Research, a journal of the American Association for Cancer
Research.

“These fat-derived stem cells could be exploited for
personalized cell-based therapeutics,” said the study’s
lead investigator, Cestmir Altaner, Ph.D., D.Sc., an associate
professor in the Cancer Research Institute of the Slovak Academy of
Sciences in Bratislava. “Nearly everyone has some fat tissue
they can spare, and this tissue could be a source of cells for
cancer treatment that can be adapted into specific vehicles for
drug transport.”

Mesenchymal stem cells help repair damaged tissue and organs by
renewing injured cells. They are also found in the mass of normal
cells that mix with cancer cells to make up a solid tumor.
Researchers believe mesenchymal stem cells “see” a
tumor as a damaged organ and migrate to it, and so might be
utilized as a “vehicle” for treatment that can find
both primary tumors and small metastases. These stem cells also
have some plasticity, which means they can be converted by the
micro environment of a given tissue into specialized cells, Altaner
says.

After extracting the stem cells from human fat tissue the
researchers worked to find a less toxic way to treat colon cancer
than the standard-of-care chemotherapy agent, 5-fluorouracil
(5-FU), which can produce toxic side effects in normal cells. They
expanded the number of mesenchymal stem cells in the laboratory and
then used a retrovirus vector to insert the gene cytosine deaminase
into the cell. This gene can convert a less toxic drug,
5-fluorocytosine (5-FC), to 5-FU inside the stem cells, and
the chemotherapy can then seep out into the tumor, producing a
lethal by-stander effect.

In nude mice – animals with an inhibited immune system
– engrafted with human colon cancer, the researchers first
injected the engineered mesenchymal stem cells, then 5-FC. They
found tumor growth was inhibited by up to 68.5 percent in the
animals, and none of the mice exhibited any signs of toxic side
effects.

However, none of the animals remained tumor-free. “The
procedure was quite effective even though we applied the stem cells
just once. Obviously, repeated treatment will increase the
efficacy, as would using this strategy in combination with other
treatments,” Altaner said.

Normal mesenchymal cells can be isolated from various sources,
including bone marrow, but the yield is not nearly as great as what
the researchers derived from fat tissue. Removal of fat
tissue during surgery to remove a tumor would be simple, says
Altaner. Liposuction could also be used to isolate mesenchymal stem
cells can also be gathered and isolated through liposuction, and
the cells frozen in liquid nitrogen for future therapeutic use.
Both processes would be easier than taking bone marrow from a
patient, Altaner said.

The study was funded by grants from the Slovak Academy of
Sciences and the League Against Cancer, and support from the
Slovakian national cancer genomics program.

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